Variations in EEG and motor functions related to COMT gene in patients with fibromyalgia

Abstract

[eng] Fibromyalgia (FM) is a chronic syndrome characterized by widespread pain, fatigue, unrefreshing sleep, somatic complaints, and affective and cognitive alterations. Although there is recent evidence indicating that negative affect may play a relevant modulatory role for the maintenance of fibromyalgia symptoms, little is known about how genetic polymorphisms may influence motor function, sleep and affective processing in fibromyalgia. The major goal of the present thesis was to analyze the influence of the val158met polymorphism of the COMT gene which is associated with the enzymatic activity level of cathecolamine degradation on gait and balance, sleep and emotional regulation. For this purpose, a multidisciplinary approach taking into account biomechanical parameters of motor function and parameters of the brain activity during sleep and during affective processing was used to compare individuals displaying either low (met homozygotes) or high COMT activity (val carriers). Motor function was assessed by analyzing gait and balance through video recordings in healthy controls and FM patients (study 1). In addition, two subsamples of FM patients based on the val158met polymorphism participated in a night polysomnography recording (study 2) and an experimental task with presentation of startle noise stimuli when viewing affective pictures (study 3). Study 1 showed that FM patients display a significant reduction in gait parameters such as speed, step length and full step, cadence and etc., as well as deficits in postural control and balance. Study 2 revealed that FM patients with low-activity of the COMT enzyme appear to be more physically impacted and depressed, and to have poorer quality of sleep (greater number of awakenings during the night, longer in bed and more fragmented sleep during REM) than FM patients with high-activity of the COMT enzyme. Finally, Study 3 showed that patients with low-activity of the COMT enzyme display significant alterations of the early components of the event-related brain potentials elicited by pleasant and unpleasant stimuli as compared with FM patients displaying high COMT activity. These studies suggest: 1) that gait and balance are altered in patients with FM compared to pain-free controls, and 2) that sleep and affective processing in FM patients may be modulated by the val158met polymorphism of the COMT gene that regulates the enzyme activity of catecholamines. In summary, these findings provide further support for the notion that FM symptoms would require multidimensional assessment and intervention to provide optimal conditions for improving quality of life in these patients. Moreover, our findings underline the relevance of considering genetic and neurofunctional markers for a complete understanding of fibromyalgia.